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1. The Importance of Tissue Banking and Tissue Research:Presentation on May 5, 2004 at“Conflicts of Interest, Privacy/Confidentiality, and Tissue Repositories: Protections, Policies, and Practical Strategies”
3. “Eye on the Prize”Improve the public’s health Conduct biomedical research to increase knowledge and understanding of biological processes.
Respect subjects’ rights and personal autonomy; minimize harm.
4. Use of Human Biological Materials in Research Human subject protections are applicable not only to clinical trials but also to the use of human biological materials in research studies, including basic science projects.
5. Human Biological Materials HBMs Click and type your text hereClick and type your text here
6. Repositories Tissue banks
Stored blood/urine samples
Freezers containing HBMs under individual control of principal investigators
Histologic slide files
Eiseman, E. and Haga, Susanne B., “Handbook of Human Tissue Sources,” Rand, 1999.
7. Requirements of Repositories Security of samples
IRB oversight
Record keeping for informed consent
Confidentiality
Anonymize samples
Increased workload !!
8. Challenges Educating researchers
Use of previously archived HBMs that were obtained without consent
Re-use of HBMs
Utility of anonymized samples
Utility of autopsy specimens
Assessment of risk by IRBs:
What is genetic research?
Is “genetic” research necessarily high risk?
Demands on Tissue Repositories
9. Educating Researchers Clinical research
Translational research
Basic science research
What is a Repository?
10. Anonymized Samples Value in basic science studies
Disadvantages for translational/clinical research
Studies not optimal
Inability to perform long-term follow-up or prognostic studies
Inability to request more of the same sample or different samples that don’t duplicate the original
Clinically useful information cannot be conveyed (rare)
11. Classifying HBMs:Assessment of Risk Click and type your text hereClick and type your text here
12. Use of HBMs in “Genetic” Research:Assessment of Risk Germline
Inheritability
Implications for immediate and extended family
Implications for ethnic group
Use of “normal” tissues
Somatic cell- less risk
Acquired mutations
Use of diseased tissues
No implications for family
13. Classifying HBMs:Assessment of Risk Click and type your text hereClick and type your text here
14. HBMs in Research David Korn, “Contribution of the Human Tissue Archive to the Advancement of Medical Knowledge and the Public Health,” in “National Bioethics Advisory Commission Report on Research Involving Human Biological Materials: Ethical Issues and Policy Guidance,” Volume II, January 2000.
15. HBMs in Research: Early History Birth of the discipline of pathology: Autopsies performed by physicians on their deceased patients- Renaissance Italy
Origin of the science of pathology: systemic study of the causes, mechanisms and natural history of diseases- 19th century Germany- Rudolph Virchow- the application of light microscopy to the study of diseased HBMs and the “cell theory of disease”
16. HBMs in Research Historical use of archived specimens
Re-use of specimens
Pathologists and the histological slide file
Increased demand for tissues
Tissue microarrays
Gene expression arrays
17. Re-use of Archived Specimens DES:
1960s: Robert Scully at MGH
Unusual tumor of the vagina- “clear cell adenocarcinoma of the vagina”
Mothers had been treated with the nonsteroidal estrogenic hormone diethylstilbestrol during their pregnancies
Establishment of a national registry
Early detection and cure rate of 90%
18. Re-use of Archived Specimens Hepatic Angiosarcoma
1940s-1950s: recognition of carcinogenic potential of occupational and environmental agents from suspicions of a pathologist observing small clusters of unusual neoplasms and thinking about shared histories
Plastic starting materials: vinyl chloride and polyvinyl chloride
Thorotrast (contrast agent)
19. Re-use of Archived Specimens Bronchopulmonary Neoplasia
Oscar Auerbach, East Orange, NJ
Histopathological changes in the lungs of autopsied smokers compared to lung cancer
New York Times obituary: “pathologist who found the first evidence in human lung tissue of a link between cancer and smoking”
20. Archived Specimens Uranium Mining
Geno Saccomanno
Archive of pulmonary pathological and cytological specimens from underground uranium workers
Bronchogenic carcinoma
Apply direct, rapid modern detection technologies for candidate markers to existing specimens
21. Autopsy Specimens: Brain Prion Diseases
Cognitive Dementia
Altzheimer’s disease
22. Molecular Genetic Methods Lymphomas:
Sklar and Cossman- 1970s
Knowledge of normal genetic maturation of lymphocytes into immunocompetent cells
Proliferative lymphoid lesions bearing different histopathologic diagnoses
Fixed and frozen tissue collections
23. Molecular Virology Viral Neoplasias
Burkitt’s Lymphoma: childhood lymphoma prevalent in central Africa
1970s- Epstein and Barr show that Burkitt’s lymphoma cells harbor a virus
Infectious mononucleosis
Link between infectious mononucleosis and Hodgkin’s lymphoma
24. Molecular Virology Human Papilloma Virus (HPV)
Pap smears and collections of specimens
Sequential patterns of progression from normal to dysplastic to neoplastic changes in cervical epithelial cells
HPV difficult to culture
New diagnostic molecular tests for “aggressive” subtypes
25. Molecular Virology Influenza
AFIP in 1990s
Samples of autopsied lung tissue from 198 soldiers who died of the “Spanish Flu” in 1918
Understanding lethality
Similarity to modern strains
26. Molecular Virology HantaVirus
1993 cluster of deaths in the American Southwest
Suspicious clinician, astute epidemiologist, observant Navajo elders, and specimen archives
CDC libraries of viruses, viral proteins and serum specimens
Pulmonary tissues from the autopsied victims
27. Molecular Genetic Methods APC gene: adenomatous polyposis coli
Frozen specimens of colorectal cancers
Banked DNA specimens from patients with familial adenomatous polyposis
Chromosome 5q
28. Molecular Genetic Methods:Cancer Genome Anatomy Project 1997- CGAP launched by NCI
Classify tumor genes by the type of cancer cell they come from and by degree of malignancy
Comprehensive molecular characterization of cancer and precancerous cells
29. Conclusion (Korn Report): “Now more than ever before, the dramatic growth of the biomedical knowledge base and the applicability of powerful new technologies to tiny samples of diseased human tissues offer promise of major breakthroughs in understanding – and effectively managing- some of the most intractable diseases of humankind. (cont’d)
30. Conclusion (Korn Report): To achieve that promise, public policy must continue to encourage the accumulation of the human tissue archive and facilitate its accessibility for medical research.”